Impact of HIV Co-Infection on Clinical Presentation in Patients with TB and Correlation of the Findings with Level of Immune Suppression.

Background
The Human Immunodeficiency Virus (HIV) has long been known to alter the clinical presentation of tuberculosis (TB), which varies according to the time of occurrence of TB infection and the level of immunodeficiency. Identifying variations in clinical features in HIV-TB coinfection might be helpful in settings with limited diagnostic facilities. The aim of this study was to assess the clinical presentation of TB in HIV coinfection and associate clinical findings with level of immune suppression (CD4 count).


Materials and Methods
In this prospective, cross-sectional observational study 110 patients having TB-HIV co-infection were assessed for clinical presentation and correlation with CD4 count. The study setting was a tertiary care teaching hospital. Patients were categorized in three group based on CD4 counts as group I: ≤ 100 cells/cmm, group II: 101-200 cells/cmm and group III: > 200 cells/cmm.


Results
110 patients were enrolled, 70% had CD4 cell count < 200 cells/mm3. Mean age and CD4 cell were 33.82±8.79 years and 181.7cells/cmm, respectively. Most common form of tubercular involvement was pulmonary (56.4%) followed by combined pulmonary and extra-pulmonary involvement (28.2%) and exclusively extra-pulmonary (15.5%). No significant intergroup difference was observed in site of involvement among three groups (p=0.700). Cough (91.8%) followed by low grade fever (85.5%), anorexia (82.7%) and weight loss (66.4%) were the commonest presenting symptom without any significant inter group difference. 70.9% patients were in undernourished category and 53.6% were febrile on examination. Sputum negative TB was noted 53.8%. 72.0% of patients with CD4 counts ≤100 had sputum negative TB as compared to sputum positive TB (28%).


Conclusion
Due to varied clinical presentation of TB in HIV patients, ample knowledge of the clinical spectrum at different levels of immunosuppression is absolutely necessary to identify such patients early.


INTRODUCTION
Tuberculosis (TB) is the leading cause of death from any single pathogen worldwide. This situation has worsened following advent of the Human Immune deficiency Virus (HIV) pandemic, leading to a dramatic increase in the number of TB cases globally (1). HIV and TB have long been known to have a close and complex association, with each having the potential to alter the TANAFFOS natural course of the other. The term 'co-epidemic' or 'dual epidemic's is often used to describe their relationship. Also referred as "cursed duet" or "deadly duo", this dual epidemic is becoming a continuously increasing global emergency especially in the developing and underdeveloped countries (2). There exists a harmful HIV-infection is the strongest risk factor for progression of latent TB infection to active disease (4).
About a third of the human population is estimated to be latently infected with Mycobacterium TB (M. tuberculosis) but the lifetime risk of active TBTB is only 5-10% in persons with TB infection alone, whereas the annual risk of active TB is 5 to 15% in persons co-infected with HIV and TB. It is estimated that about 60-70% of HIV positive persons will develop TB in their lifetime (1). Patients with co-infection also have a higher case fatality rate and lifetime risk is above 30%. HIV is one of the most important factors contributing to the increased incidence of TB globally (4) due to either primary infection (8), reinfection (4,9), increasing the risk of progression from one stage of TB to the next, or progression from latent infection (clinically quiescent) to clinical disease (reactivation) (10), as control of TB in an individual depends on an intact cellular immune response (11). TB itself can also accelerate the course of HIV infection by lowering the CD4 cell count (12) and increased HIV replication at sites of disease affected by TB such as lung parenchyma and pleural fluid (13).
Immune control of M. tuberculosis depends on both innate and adaptive cell-mediated immunity (14).
Untreated HIV infection has been known to weaken the immune system either by severely depleting the CD4 cells (15) or by CD4 T-cell dysfunction as evidenced by reduced IL-2 or IFN-c production (16), and this in turn increases susceptibility to infections, including TB. Thus, the incidence of TB in HIV-infected patients is closely correlated to the severity of immunosuppression (17).

Ethical Statement
Ethical clearance for the study was obtained from the Institutional ethical committee approved the study protocol. Written informed consent obtained from all the patients before participation in to the study.

Statistical Analysis
Continuous data was presented as mean (±SD) and categorical data was presented as frequency and percentages.

RESULTS
In total 110 patients with co-infection of HIV and TB, most patients (42.7%) had CD4 counts between 101 to 200 ( Figure 1). Compared to females, males were affected more frequently with significant difference observed amongst groups (p=0.013), while the duration of combined illness did not vary significantly among the groups ( Table 1). The demographic and essential medical history characteristics (      (40).
The strengths of our study include analysis of clinical TB and also assessing these presentations across a resolution of CD4 strata than has not been previously published. A unique feature of our study was the assessment of clinical presentation of TB, whether pulmonary, extrapulmonary or combined, varying with the level of immune-suppression and correlation of these findings with CD4 levels, a feature previously not described.
Our study has some limitations also, including bias in patient selection. As our centre is a referral centre for the region, it is highly likely that patients with TB seen here, have more severe or clinically advanced disease due to